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rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0017768,
umls-concept:C0025260,
umls-concept:C0026336,
umls-concept:C0030664,
umls-concept:C0185117,
umls-concept:C0285890,
umls-concept:C0719517,
umls-concept:C0927232,
umls-concept:C1522424,
umls-concept:C2349182,
umls-concept:C2911684
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pubmed:issue |
29
|
|
pubmed:dateCreated |
2011-7-20
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|
pubmed:abstractText |
Emerging genetic and clinical evidence suggests a link between Gaucher disease and the synucleinopathies Parkinson disease and dementia with Lewy bodies. Here, we provide evidence that a mouse model of Gaucher disease (Gba1(D409V/D409V)) exhibits characteristics of synucleinopathies, including progressive accumulation of proteinase K-resistant ?-synuclein/ubiquitin aggregates in hippocampal neurons and a coincident memory deficit. Analysis of homozygous (Gba1(D409V/D409V)) and heterozygous (Gba1(D409V/+) and Gba1(+/-)) Gaucher mice indicated that these pathologies are a result of the combination of a loss of glucocerebrosidase activity and a toxic gain-of-function resulting from expression of the mutant enzyme. Importantly, adeno-associated virus-mediated expression of exogenous glucocerebrosidase injected into the hippocampus of Gba1(D409V/D409V) mice ameliorated both the histopathological and memory aberrations. The data support the contention that mutations in GBA1 can cause Parkinson disease-like ?-synuclein pathology, and that rescuing brain glucocerebrosidase activity might represent a therapeutic strategy for GBA1-associated synucleinopathies.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/21730160-11176955,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21730160-11493715,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21730160-12438441,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21730160-12709427,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/21730160-15525722,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/21730160-16449387,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/21730160-18852351,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21730160-18987351,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21730160-19094956,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21730160-19286695,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21730160-19296921,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21730160-19433657,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/21730160-20643691,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21730160-20673762,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21730160-20801700,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21730160-20838799,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21730160-20971030,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21730160-21257328,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21730160-21472771,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21730160-3924448,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21730160-5338605,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21730160-7097276,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21730160-9278044,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21730160-9661800
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1091-6490
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pubmed:author |
pubmed-author:ChengSeng HSH,
pubmed-author:ClarkeJenniferJ,
pubmed-author:GrabowskiGregory AGA,
pubmed-author:KinnecomCathrineC,
pubmed-author:LiLingyunL,
pubmed-author:PassiniMarco AMA,
pubmed-author:SardiS PabloSP,
pubmed-author:SchlossmacherMichael GMG,
pubmed-author:ShihabuddinLamya SLS,
pubmed-author:SidmanRichard LRL,
pubmed-author:StanekLisa MLM,
pubmed-author:TamsettThomas JTJ
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pubmed:issnType |
Electronic
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pubmed:day |
19
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pubmed:volume |
108
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
12101-6
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pubmed:meshHeading |
pubmed-meshheading:21730160-Analysis of Variance,
pubmed-meshheading:21730160-Animals,
pubmed-meshheading:21730160-Blotting, Western,
pubmed-meshheading:21730160-Dependovirus,
pubmed-meshheading:21730160-Endopeptidase K,
pubmed-meshheading:21730160-Gaucher Disease,
pubmed-meshheading:21730160-Gene Transfer Techniques,
pubmed-meshheading:21730160-Genetic Vectors,
pubmed-meshheading:21730160-Glucosylceramidase,
pubmed-meshheading:21730160-Hippocampus,
pubmed-meshheading:21730160-Immunohistochemistry,
pubmed-meshheading:21730160-Mice,
pubmed-meshheading:21730160-alpha-Synuclein
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pubmed:year |
2011
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pubmed:articleTitle |
CNS expression of glucocerebrosidase corrects alpha-synuclein pathology and memory in a mouse model of Gaucher-related synucleinopathy.
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pubmed:affiliation |
Genzyme Corporation, Framingham, MA 01701, USA. pablo.sardi@genzyme.com
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pubmed:publicationType |
Journal Article
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